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治病新法:用细菌对付细菌
http://www.100md.com 2000年10月1日 HealthSCOUT Reporter
     Germ vs. Germ

    WEDNESDAY, Sept. 27 (HealthSCOUT) -- Using germs to fight germs, researchers in Italy have engineered a new weapon that may some day stop infections right where they start.

    Italian researchers slipped new genes into bacteria that live in your mouth and genital tract, giving them the ability to manufacture poisons that kill yeast infections. The genetic engineering may one day help doctors prevent other kinds of infections in the mouth, stomach and vagina.
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    "What we did was to engineer a human commensal bacteria, which can be found in oral or vaginal mucosa," says Luciano Polonelli, a professor of microbiology at the Università degli Studi di Parma in Italy. Commensal bacteria are germs that naturally live in wet and warm places in the human body and are either helpful or at least cause no harm. "It seems these organisms are well-adapted to being genetically manipulated," he says. The scientists put a gene into the bacteria that could trigger some antibiotic activity.
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    Polonelli's research builds on studies showing that genetically altered bacteria could produce natural antibiotics. "Our previous research showed that this [alteration in the gene]… mimicked that activity of a killer toxin produced by [other types of] yeast," Polonelli says. He tested his altered bacteria in rats.

    The killer toxin proved itself powerful against Candida albicans, normally part of the body's flora. When this species of fungi overgrows, it can cause vaginal yeast infections in women and thrush, the sore throat infection that is especially a common problem in people infected with HIV, the virus that causes AIDS. Polonelli's problem was that altering the gene was expensive and difficult. Also, the portions of it that could trigger an antibiotic action were unstable, which made them difficult to use.
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    "What is new, now, is that we have introduced the gene encoding for the antibiotic activity directly into a bacteria that always lives in the mucous of the vagina," Polonelli says. "The bacteria Streptococcus gordonii colonizes the vagina and can produce antibody until the infection is killed."

    To test how well the strep bacteria worked, Polonelli put the engineered germ into the vaginas of rats who had been deliberately given a yeast infection. Within three weeks, 75 percent of the rats treated with the new germ were cured of the infection. "The bacteria grows and colonizes and produces these antibodies with antibiotic activity," Polonelli explains. "It eradicated Candida albicans and the bacteria can continue to secrete the antibodies until the Candida disappears."
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    The results were published in the October issue of Nature Biotechnology.

    "This is a very exciting strategy," says Kevin Whaley, a professor at Johns Hopkins University in Baltimore, and the director and research scientist at Epicyte Pharmaceutical in San Diego. "Unlike antibiotics in pills, we are truly talking about preventing transmission of infectious disease at the first interface with our bodies, the mucosal surfaces." Epicyte is doing research in similar areas as Polonelli.
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    Whaley says interest in using engineered germs to kill disease has received a shot in the arm because of AIDS and other sexually transmitted diseases. "There is increasing interest in mucosal surfaces, because these moist environments are where most infections happen. About 90 percent of infectious disease is passed across mucous membranes," he says.

    Whaley says genetically altering germs that live naturally in the body could also be a way of getting a vaccine. "You could take a piece of protein from some virus and put it into a bacteria," he says. "The bacteria would then produce an antigen, and that antigen stimulates your immune system into protecting you from that particular disease."
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    What To Do

    Both Whaley and Polonelli say it will be a while from testing the engineered bacteria in rats to using it in humans. "Our first step is in the animal models," Whaley says. "If it's safe, we need to produce it in sufficient quantities, and then we proceed to a clinical safety trial in a larger number of animals. That could lead to a small test in humans, and then a much larger test."

    "At least 10 years," Polonelli says. "It's just an experimental model at the moment. Hopefully, it can be safely used in human beings for clinical trials. We are working on that now.", 百拇医药